About

The Personalised Cancer Medicine Program at Karolinska Institutet

The Personalized Cancer Medicine (PCM)-program is a “meta-research” project at Karolinska Institutet, (KI). 

PCM is an interdisciplinary research platform and the main focus is to strengthen the infrastructure for local, national and international team science addressing PCM. 

It operates in order to join forces with KI, Karolinska University Hospital (K) and Science for Life Laboratory (SciLife Lab) to establish PCM as a leading treatment concept in academic cancer healthcare in Stockholm. 

It also serves the local contact point for collaborations with major cancer centres in Europe in the organization Cancer Core Europe.

The PCM Program is generously supported by The Cancer Research Funds of Radiumhemmet.

Action points in Summary

Within this general aim, these are the most important action points:

  • to enhance the local machinery for early clinical trials (phase 0-II) 
  • to optimize the collaboration with Cancer Core Europe (CCE)
  • to support the development of bioinformatics support and clinical decision tools
  • to find solutions for local, national and international data-sharing
  • to exploit modern diagnostic imaging technologies for PCM-research
  • to involve patient representatives and utilize patient self-reported data

The PCM program has been instructed not to provide direct support to ordinary PI-driven research projects within PCM or create its own (long term)  infrastructural units.

History 

The PCM program was an initiative taken by clinical researchers in 2012. In 2014 KICancer was contracted by Radiumhemmets Research Funds to act as a KI umbrella for the program. The program also works within the Karolinska University Hospital (K), organized under the regional health authorities and with the Science or Life laboratory (SciLifeLab), which is a national facility for HTP/-omics analysis with a KI branch. A most important operation is to bring together scientists at KI and SciLifeLab with clinicians at K for PCM team science.

Karolinska Institutet is a medical university. Cancer research makes up 25% of the volume of research, including clinical research, biomedical research, epidemiology and nursing/health science. Approximately 160 groups in 15 of our 22 departments pursue cancer research full-time or partiallly. The cancer research is represented at the University level by trans-departmental organizations, KICancer Researchers network (KICancer, 2003 -2019), StratCan (2010-2019) and now Cancer Research KI (2019 -).

Organization and Management

Since April 2019 the PCM program is formally organized under a working group (WG 4, chaired by Ingemar Ernberg) within the new common organization “Cancer Research KI”. 

The current organization structure is as follows, where the Task Forces (TF) are mirroring similar task forces within Cancer Core Europe (CCE).

The steering group makes decisions on strategies and key issues. The steering group chair is also operative as the grant receiving PI for the program. The steering group interacts with the reference group both in terms of mutual dissemination of information and advice on decisions. The operative work is handled by the executive group together with its TFs and the executive expert team (those partly financed by the PCM-program as listed below, table 1; appendix 1). The program director leads and coordinates the daily work, facilitates and follows up on decisions and prepare future activities, in collaboration with the chair/PI. The director reports to the steering group.

Since early 2016 the PCM program, with one of its main foci on PCM early clinical trials, has been closely collaborating through the Karolinska University Hospital (K) and its Centre for Clinical Trials (CKC). The head of CKC’s unit for early clinical trials (oncologist Jeffrey Yachnin) has a 20% assignment with the PCM program. The PCM program also co-finances the local principal investigator (PI) for the Basket of Basket (BoB)-trial (oncologist Luigi De Petris), part of a research nurse at CKC as well as a pilot study, with Jeffrey Yachnin as PI, on the establishment of liquid biopsies for biomarker screening as a method to match late stage cancer patients to early clinical trials.

Apart from K, the PCM program interacts with other key hospitals for cancer care in the region, the breast cancer team at the South Hospital (Södersjukhuset) (via Johan Hartman) and the Prostate cancer team at Capio St Göran´s Hospital (Johan Lindberg/Henrik Grönberg).

The PCM program interacts closely with Genome Medicine Sweden (GMS) and its initiator professor Richard Brandell-Rosenquist, who is a member of the PCM reference group.

We are also connecting to the national Participatory PCM (PPCM) program of the Sjöberg´s foundation at the Royal Academy of Sciences (KVA) through its local Stockholm node (via Simon Ekman, oncologist).

The Karolinska CCC has just been  accredited by OECI in April 2020. The CCC will be a joint venture between the K Theme Cancer and the Cancer Research KI and is thought of as an umbrella for development of cancer care and integration of preclinical and clinical cancer research. It is planned that the PCM program shall be an integrated important partner in the CCC.

Cancer Core Europe

International task forces and biomarker-guided trial

The membership in the Cancer Core Europe (CCE) has so far been highly instrumental for the local PCM program. CCE is a legal association (since 2017) of seven leading cancer centers in Europe, with the major mission to create a critical mass of translational cancer research (particularly through clinical trials and translational research). Its Basket of Basket (BoB) trial started during 2018 where KI/K joined with the first genomic screening of patients during the summer of 2019. More modules are starting during 2020. In addition, KI has developed the MTB portal, a clinical decision support tool that unifies the interpretation of the genomics data across CCE centers and provides the framework to exchange and harness the results. The PCM program has harmonized its organization with the CCE workflow by establishing TFs in the same areas.

To learn from leading centers we have made study visits to NCT, Heidelberg and at Gustave Roussy, Paris, as well as invited speakers from DKFZ (Dirk Jäger and Hanno Glimm), Gustave Roussy (Lex Eggermont), VHIO, Barcelona (Rodrigo Dienstmann) and Rigshospitalet, Copenhagen (Ulrik Lassen; appendix 3).

Ingemar Ernberg, chair of the PCM program has been a member of evaluation committees of the translational cancer research both at DKFZ, Heidelberg and the German Consortium, DTKT. He has also participated in two (“Gago”-) meetings organized by the European Academy of Cancer Sciences (EACS) in Porto and in the Vatican Rome 2019, dealing with the plans for the Horizon 2030 Cancer Mission.

The main reasons for the establishment of the PCM program was the growing knowledge on complexity of cancer and the existence of a large number of subgroups and that these conditions called for a strong infrastructure promoting team science. Local and national collaboration was considered important but not sufficient enough for effective PCM research. Therefore, at an early stage, collaboration with Cancer Core Europe (CCE) was prioritized.

CCE has become an emrging model to link basic/preclinical research with early clinical research, while at the same time creating the critical mass needed for developing PCM. The PCM program serves as local node for the KI/K/SciLifeLab collaboration with CCE.

To facilitate the work with CCE, the PCM program has, since 2017, hired a local CCE-coordinator, Christina von Gertten, who is also part of the PCM-program’s executive group. CvG also handles the instrumental contacts with the ethical and legal groups at the CCE centers, as well as with local KI’s and K´s officers for legal affairs (IDL Torre Abaurrea, legal counsel).

The first priority of CCE has been to get the first common clinical trial started, the BoB trial, which is a unique personalized cancer medicine trial effort of its kind in Europe. To get started with BoB locally, two oncologists, Luigi De Petris, who is the local principal investigator, and Jeffrey Yachnin, who is head of the early clinical trial unit and subinvestigator, are since October 2017 partially financed by the PCM program (20%).

Achievements

The major focus has been:

– Establishment of the PCM program with broad connections within KI, K, SciLifeLab and other healthcare and academic institutions nationally and abroad.

– Identification of and collaboration with infrastructure of central importance for local PCM research.

– Providing support to PCM focused clinical trials by managing K/KI participation, funding of strategic key personnel positions and development of IT infrastructure.